From the Global Brain Health Institute (A.M.G.), University of California, San Francisco; Cognitive Neuroscience Center (A.M.G.), Universidad de San Andrés, Buenos Aires; National Scientific and Technical Research Council (CONICET) (A.M.G.), Buenos Aires, Argentina; Departamento de Lingüística y Literatura, Facultad de Humanidades (A.M.G.), Universidad de Santiago de Chile; Memory and Aging Center (A.E.W., M.L.M., S.L., J.D., B.M.R., D.L.L.P., B.L.M., W.S., M.L.G.-T.), Department of Neurology, University of California, San Francisco; Department of Communication Sciences and Disorders (M.L.H.), University of Texas at Austin; Department of Communication Sciences and Disorders (S.L.), Adelphi University, Garden City, NY; Cognitive Neurology and Aphasia Unit (M.J.T.P.), Centro de Investigaciones Médico-Sanitarias (M.J.T.P.), University of Malaga; Instituto de Investigación Biomédica de Málaga - IBIMA (M.J.T.P.), Malaga; Area of Psychobiology (M.J.T.P.), Faculty of Psychology and Speech Therapy, University of Malaga, Malaga, Spain; Sección Neurología (D.L.L.P.), Departamento de Especialidades, Facultad de Medicina, Universidad de Concepción, Chile; Centre for Neuroscience of Speech (A.P.V.), Department of Audiology & Speech Pathology, The University of Melbourne; and Redenlab (A.P.V.), Melbourne, Australia.
Neurology. 2022 Aug 2;99(5):e500-e511. doi: 10.1212/WNL.0000000000200750. Epub 2022 May 27.
Motor speech function, including speech timing, is a key domain for diagnosing nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Yet, standard assessments use subjective, specialist-dependent evaluations, undermining reliability and scalability. Moreover, few studies have examined relevant anatomo-clinical alterations in patients with pathologically confirmed diagnoses. This study overcomes such caveats using automated speech timing analyses in a unique cohort of autopsy-proven cases.
In a cross-sectional study, we administered an overt reading task and quantified articulation rate, mean syllable and pause duration, and syllable and pause duration variability. Neuroanatomical disruptions were assessed using cortical thickness and white matter (WM) atrophy analysis.
We evaluated 22 persons with nfvPPA (mean age: 67.3 years; 13 female patients) and confirmed underlying 4-repeat tauopathy, 15 persons with semantic variant primary progressive aphasia (svPPA; mean age: 66.5 years; 8 female patients), and 10 healthy controls (HCs; 70 years; 5 female patients). All 5 speech timing measures revealed alterations in persons with nfvPPA relative to both the HC and svPPA groups, controlling for dementia severity. The articulation rate robustly discriminated individuals with nfvPPA from HCs (area under the ROC curve [AUC] = 0.95), outperforming specialist-dependent perceptual measures of dysarthria and apraxia of speech severity. Patients with nfvPPA exhibited structural abnormalities in left precentral and middle frontal as well as bilateral superior frontal regions, including their underlying WM. The articulation rate correlated with atrophy of the left pars opercularis and supplementary/presupplementary motor areas. Secondary analyses showed that, controlling for dementia severity, all measures yielded greater deficits in patients with nfvPPA and corticobasal degeneration (nfvPPA-CBD, n = 12) than in those with progressive supranuclear palsy pathology (nfvPPA-PSP, = 10). The articulation rate robustly discriminated between individuals in each subgroup (AUC = 0.82). More widespread cortical thinning was observed for the nfvPPA-CBD than the nfvPPA-PSP group across frontal regions.
Automated speech timing analyses can capture specific markers of nfvPPA while potentially discriminating between patients with different tauopathies. Thanks to its objectivity and scalability; this approach could support standard speech assessments.
This study provides Class III evidence that automated speech analysis can accurately differentiate patients with nonfluent PPA from normal controls and patients with semantic variant PPA.
运动言语功能，包括言语时程，是诊断非流利/语法障碍型原发性进行性失语症（nfvPPA）的关键领域。然而，标准评估使用主观的、依赖专家的评估，从而降低了可靠性和可扩展性。此外，很少有研究检查过经病理证实的诊断患者的相关解剖-临床变化。本研究使用独特的尸检证实病例队列中的自动言语时程分析克服了这些局限性。
在一项横断面研究中，我们进行了一项显性阅读任务，并量化了发音速度、平均音节和停顿持续时间、音节和停顿持续时间变异性。使用皮质厚度和白质（WM）萎缩分析评估神经解剖结构的破坏。
我们评估了 22 名 nfvPPA 患者（平均年龄：67.3 岁；13 名女性患者），并证实了潜在的 4 重复tau 病，15 名语义变异型原发性进行性失语症（svPPA；平均年龄：66.5 岁；8 名女性患者）和 10 名健康对照组（HCs；70 岁；5 名女性患者）。所有 5 项言语时程测量均显示 nfvPPA 患者与 HCs 和 svPPA 组相比存在改变，同时控制了痴呆严重程度。发音速度能够可靠地区分 nfvPPA 患者与 HCs（ROC 曲线下面积[AUC] = 0.95），优于依赖专家的构音障碍和言语失用严重程度的知觉测量。nfvPPA 患者表现出左侧中央前回和额中回以及双侧额上回的结构异常，包括其下的 WM。发音速度与左侧额下回和补充/运动前区的萎缩相关。二次分析表明，在控制痴呆严重程度的情况下，nfvPPA 患者和皮质基底节变性（nfvPPA-CBD，n = 12）的所有测量值均比进行性核上性麻痹病理（nfvPPA-PSP，n = 10）患者的所有测量值都有更大的缺陷。发音速度可以可靠地区分每个亚组的个体（AUC = 0.82）。nfvPPA-CBD 组的额区皮质变薄比 nfvPPA-PSP 组更广泛。
自动言语时程分析可以捕捉到 nfvPPA 的特定标志物，同时有可能区分不同 tau 病患者。由于其客观性和可扩展性；这种方法可以支持标准的言语评估。
本研究提供了 III 级证据，表明自动言语分析可以准确地区分非流利型 PPA 患者与正常对照和语义变异型 PPA 患者。
